Capsule:
We discuss how therapeutic decisions should be shared with women who have deep endometriosis after a comprehensive evaluation; an in depth and realistic review of the benefits and risks should be made clearly available.

Deep endometriosis is a demanding condition that is associated with infertility. However, evidence supporting a direct link between deep endometriosis and infertility is weak. In fact, infertility in affected patients is more likely to be explained by the strong association between deep endometriosis and adhesions, superficial endometriotic implants, ovarian endometriomas, and adenomyosis. The purported beneficial effects of surgery on infertility are mainly based on the 40%–42% pregnancy rate (PR) after surgery observed in published case series. However, this level of evidence is questionable and overestimates the benefits of the intervention. Even if comparative studies are lacking, IVF may be a valid alternative. The procedure may be less effective in affected women compared with other indications and it is not without additional deep endometriosis-related risks. Some case reports suggest that lesions might progress during IVF causing ureteral or intestinal complications or can decidualize during pregnancy causing intestinal perforation, pneumothorax, and pelvic vessels rupture. Finally, in the decision-making process, physicians should also consider that women with a history of deep endometriosis may face an increased risk of pregnancy complications. In conclusion, clear recommendation for the management of infertile women with deep endometriosis cannot be extrapolated from the literature. The therapeutic decision should be based on a comprehensive evaluation that includes clinical history, instrumental findings, pain symptoms, risks of pregnancy complications, and the woman’s wishes.

We read with great interest the extremely good article of Somigliana
and Garcia-Velasco (1) focusing on the relationship between infertility and deep
endometriosis, and the therapeutic strategies that could be considered. They
thoroughly discuss whether or not young patients with deep endometriosis actually
need surgery, however less extensively their need of IVF to conceive.

We agree that pregnancy rates (PR) in the series of patients managed by surgery cannot entirely be attributed to the surgical procedure, and several patients would have probably been pregnant even if the surgery had not been performed (1). Moreover, authors reporting the benefit of surgery on fertility should justify the existence of preoperative infertility, even though those patients were managed for stage 4 endometriosis, in which negative impact on spontaneous conception should no longer be demonstrated. Conversely, infertility in the series of patients managed
by primary IVF does not need to be proven, because “case series of IVF are more
informative than those of surgery », as « all observed pregnancies could
be attributed to the procedure itself. »(1)

In our opinion, the questions should be
asked differently: What is the likelihood of pregnancy for a young patient with
deep endometriosis and pregnancy desire by primary IVF or surgery? (2) Does a
woman have more chances to be pregnant after a single or several IVF procedures
than after surgery followed or not by IVF? (2,3) Does a patient take a higher
risk by undergoing surgery or, conversely, in delaying the intervention for months
or years? (2,4) Is it less expensive to manage patients by several primary IVF
procedures or by a surgical intervention followed by spontaneous conception in
up to two-thirds of cases? (4) Is surgery definitively avoided in patients
undergoing primary IVF, or is it only postponed?

If a comparative “intention to treat” randomized trial is performed in this topic in the future, it will specifically answer each of the questions listed above.

In this way, it is interesting to review the comparative study of Bianchi et al (5)
by obtaining the lacked data about patients who conceived spontaneously. Accordingly
to the study’s design, women who spontaneously conceived were excluded from the
study, as were those who declined postoperative IVF. Thus, the results of the
study were reasonably different from those that would have been provided by an
“intention to treat” study where all pregnancies should have been taken into
account. To calculate the total PR, the number of patients who spontaneously
conceived in each arm of the trial should be considered. Data was obtained upon
request, and there were therefore 10 out of 115 patients with spontaneous
conception in the primary IVF arm, giving a spontaneous PR of 8.7%. In the
surgical arm, 18 out of 84 conceived spontaneously, resulting in a spontaneous
PR 2.5 times higher (21.4%). Thus, the overall PR is 29.6% in the primary IVF
arm vs. 51.2% in the surgical arm (P=0.003). By choosing surgery, patients from
Sao Paolo increased their chances to conceive by 66% during the study follow
up.

Recent guidelines state that « The effectiveness of surgical excision of
deep nodular lesions before treatment with assisted reproductive technologies
in women with endometriosis-associated infertility is not well established in
regard to reproductive outcomes (C) » (6). This means that surgery is not
required once IVF decision has been made, if the sole goal of treatment is to
increase PR following IVF. In daily practice, this statement is frequently
misunderstood, leading to the systematic practice of primary IVF in women with
deep endometriosis, because surgery is supposed to be of no effect in improving
the PR. In numerous young patients, severe complaints occur rapidly after interrupting
the contraceptive pill, and the diagnosis of deep endometriosis is affirmed.
Consequently, they usually seek care after a couple of months of pregnancy
attempts, and do not meet “infertility” criteria. When referred to medical
teams who recommend primary IVF, they are automatically recorded as “infertile”
and undergo IVF. On the other hand, when referred to teams where surgery is
recommended to treat both pain and manage pregnancy intention, they undergo primary surgery with or without postoperative IVF (3). Ultimately, the major clinical
outcome in all those young patients is the overall PR. To date, available data
suggest that PR would be comparable and if not higher in patients referred to medical
centers recommending surgery (2). In addition, in this latter case, deep endometriosis
is treated. The rate of severe postoperative complications is low when patients
are managed by experienced teams (in 405 patients managed for colorectal
endometriosis from 2010 to 2015 in our center there were prospectively recorded:
2.5% of rectovaginal fistulas, 0.25% leakages, 0.75% severe bladder dysfunction
over 3 months postoperatively, and only 1 patient with Clavien 4 complication).
Moreover, the rate of complications also concerns women who underwent primary
IVF in whom surgery is merely postponed for years.

As we recently exchanged at the last World Congress of Endometriosis in Sao Paolo, this exciting debate could only be closed by a large randomized trial in intention to treat
comparing primary IVF to primary surgery in women with deep endometriosis and
pregnancy wish (2).

We fully agree with the comments from Dr Roman and Dr Darwish – there is today a lack of strong data to support clearly any direction. Thus, young asymptomatic women may choose surgery -considering the low incidence of complications in experienced hands, but sometimes severe, that may requiere additional surgery- whereas symptomatic women and “not-so-young” women will be directly managed with IVF as time is their most precious asset that cannot be wasted while waiting for a spontaneous pregnancy.

New Discussion Features!

NEW! Open access free discussion forums on EVERY article in Fertility and Sterility! Just go to the issue and click on article title. You will be able to submit comments questions or share your thoughts on the paper-- Speak your mind!